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Biol Blood Marrow Transplant. 2018 Nov;24(11):2190-2196. doi: 10.1016/j.bbmt.2018.06.036. Epub 2018 Jul 7.

Pretransplant Serum Citrulline Predicts Acute Graft-versus-Host Disease.

Author information

1
Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota. Electronic address: arashidi@umn.edu.
2
Masonic Cancer Center Biostatistics Core, University of Minnesota, Minneapolis, Minnesota.
3
Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
4
Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
5
Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.

Abstract

Post-transplant biomarkers of acute graft-versus-host disease (aGVHD) and nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation (allo-HCT) have been extensively studied. However, pretransplant biomarkers may provide a greater window of opportunity to intervene. We measured serum biomarkers of various aspects of gut barrier physiology before HCT (median, day -7) and 7 and 28 days post-HCT in 95 consecutive allo-HCT recipients enrolled in an open-label biorepository protocol. Biomarkers included citrulline for total functional enterocyte mass, Reg3a for antibacterial activity of the gut, and intestinal fatty acid binding protein (I-FABP) for enterocyte turnover. Compared to 16 healthy control subjects, we demonstrated that patients came to transplant with abnormal levels of all 3 biomarkers (P < .05), reflecting residual damage from prior chemotherapy. All 3 biomarkers initially declined from pre-HCT to day +7 (more pronounced after myeloablative than reduced-intensive conditioning) followed by a recovery phase and return toward pre-HCT values by day +28. A lower pre-HCT citrulline was independently associated with a higher risk of aGVHD grades II to IV (hazard ratio, 1.32; 95% confidence interval, 1.03 to 1.69; P = .02), and this association was not specific to gut GVHD. The strongest correlate of NRM was a higher level of Reg3a at day +7 (P < .001). I-FABP did not predict transplant outcomes. In conclusion, pre-HCT serum citrulline levels identify patients at high risk for developing aGVHD. Our results suggest that pre-HCT interventions to augment the gut barrier may decrease the risk of aGVHD.

KEYWORDS:

Citrulline; Graft-versus-host disease; Gut barrier; I-FABP; Nonrelapse mortality; Reg3a

PMID:
30454871
PMCID:
PMC6251308
[Available on 2019-11-01]
DOI:
10.1016/j.bbmt.2018.06.036

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